RSR13 is a synthetic allosteric modifier of hemoglobin. It decreases the oxygen affinity of hemoglobin and augments oxygen unloading in the microvasculature which increases the oxygen diffusion gradient to the tissues. By increasing tissue oxygenation, RSR13 may reduce tumor hypoxia and enhance the cytotoxic effects of radiation therapy used to treat cancer patients with solid tumors. To test the safety, tolerance, and maximally tolerated repetitive dose of RSR13, we conducted a non-randomized, open-label, multi-center safety study in patients who received a conventional six-week course of cranial radiation therapy for glioblastoma multiforme. Patients enrolled in this study had a histologically confirmed supratentorial grade IV astrocytoma (glioblastoma multiforme). The dose of RSR13 was 100 mg/kg at a concentration of 20 mg/mL, administered over 60 minutes by continuous infusion via a central venous access device. RSR13 administration began on the first day of radiation therapy and was given so that the end of the infusion occured within 30 minutes prior to the start of radiation therapy. Two dose frequency groups, Groups A and B, with nine patients per group, were used. Patients in Group A received 100 mg/kg RSR13 every other day of radiation therapy, and patients in Group B received 100 mg/kg RSR13 every day of radiation therapy.